Better Cancer Monitoring with Cell-Free DNA. March, 2015

Transcription

1 Better Cancer Monitoring with Cell-Free DNA March, 2015

2 Forward-Looking Statements Statements in this presentation about the Company's expectations, applications of its technology, markets, launch of tests and other statements that are not historical facts are "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and are based on management's current beliefs, assumptions, estimates and projections. Actual results may differ materially from those projected in the forward-looking statements for various reasons, including risks associated with product and test development, test transfer to contracting labs, government regulation, market acceptance, limited commercial experience, dependence on key personnel, obtaining financing and other factors discussed in the Company's periodic reports filed with the Securities and Exchange Commission. Copyright 2015 Trovagene, Inc. Confidential 2

3 Our Goal To Improve Treatment Outcomes with Non-invasive Cancer Monitoring Trovagene s technology non-invasively detects and quantitates circulating tumor DNA in urine and plasma for improved disease management Copyright 2015 Trovagene, Inc. Confidential 3

4 Company Overview Precision cancer monitoring technology addresses a high unmet clinical need Enables frequent, non-invasive monitoring of oncogene mutation status, disease progression, and recurrence Numerous clinical collaborations with leading cancer centers 30+ clinical studies Expanding clinical evidence to support broad market adoption Generating health economic data necessary for appropriate reimbursement Significant patent portfolio around cell-free DNA Proprietary methods of extracting, purifying, detecting and quantifying oncogene mutations in cell-free DNA CLIA certified, CAP accredited, high complexity lab to offer diagnostic services NASDAQ: TROV $150M market cap* Molecular Diagnostic Specialist Focused on Cancer Monitoring Founded in 1999 NASDAQ listing 2012 $46M est. cash on hand (as of Feb ending) *fully diluted as of 02/10/15 Copyright 2015 Trovagene, Inc. Confidential 4

5 Experienced Leadership Team Antonius Schuh, PhD Chief Executive Officer Sorrento Therapeutics, AviaraDx, Arcturus, Sequenom PhD Pharm. Chem Stephen Zaniboni Chief Financial Officer Awarepoint, XIFIN, Sorrento Therapeutics, AviaraDx, Arcturus, Sequenom CPA BS Accounting MBA Mark Erlander, PhD Chief Scientific Officer BioTheranostics, AviaraDx, Arcturus, J&J, Scripps Research Institute BS, MS Biochem PhD Neuroscience Scientific Advisors Alberto Bardelli, PhD Paul Billings, MD, PhD Charles Cantor, PhD Matt Posard Chief Commercial Officer Carlo M. Croce, MD Riccardo Dalla-Favera, MD Gen-Probe, Biosite, Illumina BA Econ, UCSD Brunangelo Falini, MD K. Peter Hirth, PhD Rob Kelley VP, Marketing Duke Immunology, Merck, Guidant, Biosite, Siemens, Illumina BS Biology, Duke University MBA Anderson School of Business Janel Dockter VP, Product Development Hologic, Gen-Probe, The Scripps Research Institute BA Microbiology Oanh Dang, PhD VP, Business Development Sequenom, Gen-Probe, Illumina, Sirius Genomics, Zymeworks PhD Biomedical Sciences Vlada Melnikova MD, PhD VP, Research & Development Transgenomic, ApoCell, MD Anderson Cancer Center MD PhD Biological Engineering Keith McCormick VP, Sales & Sales Operations BioTheranostics, AviaraDx, Biogen Idec, Schering Plough, Dianon Systems BBA Marketing MBA Int l Business David Moskowitz, RPh VP, Investor Relations UBS, FBR, Caris & Co, Roth Capital BS Pharmacy MBA Finance Board of Directors Thomas Adams, PhD (Chair) Paul Billings, MD, PhD John P. Brancaccio, CPA Carl B. Feldbaum Gary S. Jacob, PhD Rodney Markin, MD, PhD Antonius Schuh, PhD Stanley Tennant, MD Copyright 2015 Trovagene, Inc. Confidential 5

6 Clinical Problem New Understanding of Cancer Targeted Therapies for Cancer Driven by Oncogene mutations and alterations Heterogeneous: Need for Genomic Monitoring Intra-tumor Inter-tumor (Distal) Therapies are expensive and have side effects Specific for particular biomarkers Response monitoring required Resistance develops Copyright 2015 Trovagene, Inc. Confidential 6

7 Limitations of Current Technology for Cancer Monitoring Imaging Tissue biopsy Circulating tumor cells Traditional blood markers Rough indication of tumor size No molecular information Radiation concerns for younger patients Invasive procedures, often not possible Potential for serious complications Serial biopsies increasingly not feasible Not representative of tumor heterogeneity Not representative of tumor heterogeneity Not informative of tumor dynamics Low clinical sensitivity Technically challenging Not representative of tumor heterogeneity Non-specific for cancer Low clinical sensitivity Copyright 2015 Trovagene, Inc. Confidential 7

8 Significant Market Opportunity Insufficient Imaging Tools in Oncology Still Yield Huge Market Initial Opportunity for Trovagene $12B In K 8-10 Metastatic cancer patients per year Imaging procedures received by cancer patient during first year of treatment Cancer already in advanced state No molecular data delivered $5B Potential market Source: BCC Research Copyright 2014 Trovagene, Inc. Confidential 8

9 ctdna Emerging as Preferred Analyte to Monitor Cancer Cancer is a disease of DNA defining cancer by what tissue it arose in is going to go by the boards pretty soon. Circulating tumor DNA levels showed a greater dynamic range, and greater correlation with changes in tumor burden, than did CA 15-3 or circulating tumor cells. The statistically significant correlation between mutational status and treatment response suggests oncogene mutation monitoring using urinary cell-free DNA can help clinicians rapidly determine responders from non-responders, [to] improve patient outcomes. Dr. Frances Collins, National Institutes of Health (NIH) Director, Politics on The Frontier of Science, Wall Street Journal, November 8, 2013 Sarah-Jane Dawson et. al., Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer, NEJM, Vol. 368, No. 12, March 2013 Filip Janku M.D., Ph.D et al., 2014 ASCO Annual Meeting Proceedings, a Journal of Clinical Oncology Sci Transl Med Feb 19;6(224):224ra24. N Engl J Med 2013; 368: Sci. Transl. Med. 4, 136ra68 (2012). Copyright 2014 Trovagene, Inc. Confidential 9

10 Circulating Tumor DNA (ctdna) Tumor cells Main Advantages of ctdna Captures intratumor heterogeneity Systemic overview of cancer Frequent sampling options for monitoring applications Different analyte options depending on clinical context Copyright 2014 Trovagene, Inc. Confidential 10

11 Why Urine? 15, ,000 genome equivalent 3,000 15,000 genome equivalent Plasma ctdna Urine ctdna Unlimited Volume Frequency of Testing Completely Non-invasive Convenient Copyright 2015 Trovagene, Inc. Confidential 11

12 SM Trovagene Precision Cancer Monitoring (PCM ) Platform Extraction and Isolation of ctdna Mutant Allele Enrichment Platform Agnostic Detection and Quantification 59% ctdna 2.0 ng/ul gdna 1.4 ng/ul 92% ctdna 4.9 ng/ul gdna 0.04 ng/ul Proprietary error rate detection and normalization. ~0.5µg ctdna/ 100 ml of urine fold enrichment Integration with Commercially Available Platforms Single Molecule Detection Ultra-Sensitive Detection and Quantitative Monitoring Copyright 2015 Trovagene, Inc. Confidential 12

13 Patent Portfolio Patent Families Patent Term Concentrating Urine Family bp TrNA Family Small Footprint Family Monitoring Disease Family bp TrNA Family Anion Exchange Purification Family Viral and Pathogen TrNA Families TrNA Patent Family Term 2018 US & EU Term to approx US provisional app filed Term to approx US provisional app filed Term to approx US & EU Term to approx US, EU, Canada Term to approx US, EU, JP, China, Australia, Canada, India Term to approx US provisional app filed Term to approx US provisional app filed Copyright 2014 Trovagene, Inc. Confidential 13

14 Strategy to Drive Clinical Adoption & Reimbursement QUALITATIVE QUANTITATIVE STANDARD OF CARE Stage 1 Tumor Status Demonstrate concordance of oncogene mutation status between urine and tumor tissue Clinical Utility: Determine mutational status of actionable biomarkers in urine when a biopsy is not an option. Ex. BRAF, KRAS Stage 2 Tumor Dynamics Expand mutational coverage of urine-based actionable oncogene mutations for our PCM platform Clinical Utility: Quantitatively assess mutational status in urine longitudinally as an indicator of responsiveness to therapy, disease status & emergence of resistance mutations Stage 3 Improved Patient Outcomes Demonstrate in multi-institutional trials that results from urine-based monitoring of actionable mutations increases patient progression-free survival (PFS) & overall survival (OS) Demonstrate health economic benefits of non-invasive oncogene mutation monitoring Clinical Utility: Quantitatively assess patient mutational status in urine longitudinally for mutational status and early detection of resistance to therapy as a decision tool for therapy selection $100- $200M Revenue $500+M Revenue Multi $B Revenue Copyright 2014 Trovagene, Inc. Confidential 14

15 SM 30+ Collaborations to Validate & Integrate our PCM Platform Disease Ongoing Pending Protocol in Dev/Approval Under Evaluation Market Size U.S. (# of pts) Lung Cancer (NSCLC) Colorectal Cancer Pancreatic Cancer , ,154, ,000 Melanoma ECD/LCH 2 1 5,000 Brain Cancer ,000 Prostate Cancer All-Comers, Metastatic Cancers 1 2,618, ,000 HPV 2 3 Total # of Studies Copyright 2014 Trovagene, Inc. Confidential 15

16 Current Development Program for Cancer Monitoring Applications KRAS Exon 2 BRAF V600E KRAS Exon 2,3,4 EGFR Exon 20 T790M NRAS Exon 2 NRAS Exon 2,3,4 BRAF V600E PIK3CA H1047R EGFR Exon 19 Del EGFR Exon 21 L858R ALK Rearrangements Copyright 2014 Trovagene, Inc. Confidential 16

17 Clinical Results Presented & Published To Date 4/2014 AACR Poster Concordant BRAF 5/2014 5/2014 6/2014 Publication Oncotarget Histiocytic BRAF MD Anderson Publication Blood ECD clinical guidelines 2 ASCO Presentations 1. Histiocytic BRAF MSKCC/MD Anderson 2. Longitudinal BRAF MD Anderson 8/2014 NEXTGEN DX SUMMIT Oral Presentation, Technology IPV Meeting 8/2014 Poster Presentation HR-HPV Publication 10/2014 Cancer Discovery Histiocytic BRAF Initial concordance with plasma and tissue Initial longitudinal data concordance with imaging ECD guideline 2014 Q1 Q2 Q3 Q4 Copyright 2014 Trovagene, Inc. Confidential 17

18 Histiocytic Disorders: ECD/LCH Standard of Care CLINICAL YTILITY ECD/LCH ALL STAGES Molecular diagnosis of BRAF mutation patients are placed on targeted therapy Re-staging of cancer ECD/LCH Tissue Biopsy First Line Treatment Imaging (every 2-3 months) TROVAGENE Detection BRAF V600E Monitoring Therapeutic Response BRAF V600E STUDIES MSKCC, MDACC, NIH (30 patients) Copyright 2014 Trovagene, Inc. Confidential

19 Prospective Blinded Study of BRAF V600E Mutation Detection in Cell-Free DNA of Patients with Systemic Histiocytic Disorders 1 Background Erdheim Chester disease (ECD) and Langerhans Cell Histiocytosis (LCH) are histiocytic diseases Histiocytic diseases harbor somatic mutations (i.e., BRAF V600E) Patients with BRAF V600E mutation respond to BRAF inhibitors Histiocytic tissue technically challenging for tissue biopsy Concordance: Longitudinal: Objectives Tissue biopsy (gold standard) vs. urine BRAF cfdna Urine vs. plasma BRAF cfdna Urine cfdna BRAF status during treatment regimen Study Design Urine and Plasma from patients Blinded study: tissue biopsies (CLIA) correlated after ctdna results Evaluate Tissue Biopsy BRAF V600E Concordance V600E Positive Histiocytic Patients N=30 Urine cfdna BRAF V600E Evaluate Plasma BRAF V600E Concordance Evaluate Tissue Biopsy BRAF WT Concordance V600E Negative Evaluate Plasma BRAF WT Concordance 1 Hyman et al., Cancer Discov Jan;5(1):

20 ctdna Improves Genotyping Over Tissue Biopsies in Histiocytic Patients 1 Tissue BRAFV600E genotype Urinary ctdna N=30 Plasma ctdna N=19 Indeterminate Genotype BRAF Wildtype n=9 n=6 n=15 BRAFV600E Mutant Urinary ctdna BRAFV600E genotype Trovagene Assay Results p=0.005 Trovagene Assay Results p=0.02 BRAF Wildtype n=14 n=16 BRAFV600E Mutant Initial Tissue Results Initial Tissue Results On BRAF inhibitor Wildtype Mutant Unknown On BRAF inhibitor Wildtype Mutant Unknown 1 Hyman et al., Cancer Discov Jan;5(1): % concordance between tissue, urine and plasma in treatment naive patients 20

21 Correlation between Longitudinal ctdna and Radiographic Response 1 BRAFV600E burden in urine correlates w/ radiographic response. BRAFV600E allele burden in urine changes dynamically with therapy. 1 Hyman et al., Cancer Discov Jan;5(1):

22 Dynamic Monitoring Captures Early Progression and Response 1 Successful monitoring tumor dynamics independent of drug class used Patient s tumor progressed within 1 wk of Anakinra withdrawal Demonstration of need for higher frequency urine-based testing to monitor One week Patient responded to Vemurafenib, BRAF inhibitor Demonstrates that continually monitoring patient enables optimal therapy over time 1 Hyman et al., Cancer Discov Jan;5(1):64-71 Copyright 2014 Trovagene, Inc. Confidential 22

23 NSCLC Standard of Care CLINICAL UTILTY MOLECULAR DIAGNOSIS AND RESECTABLE DISEASE Success of surgery Re-staging of cancer Adjuvant radiation/chemo or not? STAGE IV METASTATIC DISEASE Selection of correct first line therapy within days of diagnosis patients go on right treatment early (anti-egfr or Chemo?) Re-staging of cancer, response and emergence of resistance Replacement of second biopsy and selection of correct second line therapy (anti-t790m or Chemo?) NSCLC Tissue Biopsy Surgery Adjuvant Therapy First Line Treatment Imaging (every 6-8 weeks) Tissue Biopsy Second Line Treatment Imaging (every 6-8 weeks) TROVAGENE Molecular Detection EGFR Exon 19 del EGFR L858R KRAS Minimal Residual Disease Response Monitoring EGFR KRAS G12/13 Monitoring Emergence of Resistance EGFR T790M Molecular Detection & Response Monitoring EGFR T790M MARKET Primary Biopsies ~85,000 patients / year ~85,000 tests per year 15% EGFR+ 15% RAS+ Minimal Residual Disease Response ~25,500 patients x 5 ~127,500 tests per year 15% EGFR+ Monitoring Emergence of Resistance ~13,000 patients per year x 10 tests ~130,000 tests per year 60% EGFR T790M+ Molecular Detection & Response Monitoring ~7,500 patients x 10 tests ~75,000 tests per year Copyright 2014 Trovagene, Inc. Confidential 23

24 NSCLC Standard of Care CLINICAL UTILTY MOLECULAR DIAGNOSIS AND RESECTABLE DISEASE Success of surgery Re-staging of cancer Adjuvant radiation/chemo or not? STAGE IV METASTATIC DISEASE Selection of correct first line therapy within days of diagnosis patients go on right treatment early (anti-egfr or Chemo?) Re-staging of cancer, response and emergence of resistance Replacement of second biopsy and selection of correct second line therapy (anti-t790m or Chemo?) NSCLC Tissue Biopsy Surgery Adjuvant Therapy First Line Treatment Imaging (every 6-8 weeks) Tissue Biopsy Second Line Treatment Imaging (every 6-8 weeks) TROVAGENE Molecular Detection EGFR Exon 19 del EGFR L858R KRAS Minimal Residual Disease Response Monitoring EGFR KRAS G12/13 Monitoring Emergence of Resistance EGFR T790M Molecular Detection & Response Monitoring EGFR T790M STUDIES MSKCC, COH, UCSD and Catholic Health Initiatives UCSD (30 patients) MSKCC, City of Hope, UCSD and Catholic Health Initiatives (340 patients) Pharma UCSD (100 patients) Copyright 2014 Trovagene, Inc. Confidential 24

25 NSCLC Initial Biopsy: Cost Assumptions 1 Cost per Biopsy Cost per Biopsy $40,000 $30,000 $20,000 $10,000 $0 $40,000 $35,000 $30,000 $25,000 $20,000 $15,000 $10,000 $5,000 $0 Biopsy without AE ~80% Claims $8,869 Average Cost Biopsy with AE ~20% Claims $37,745 Average Cost Cost per Biopsy $40,000 $35,000 $30,000 $25,000 $20,000 $15,000 $10,000 $5,000 $0 Average Biopsy Cost $14,634 Average Cost While the median cost for a lung cancer biopsy is ~$3,750, a recent review of 5% of the Medicare population found that complications drove average biopsy cost to $14, Medicare claims analysis presented by Lokhandwala at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology mtg 25

26 Replacing Tissue Biopsy in Metastatic NSCLC with ctdna Monitoring ctdna EGFR for Treatment Response and Early Acquisition of EGFR T790M Resistance Mutation 300 Metastatic NSCLC Patients at Diagnosis, EGFR Exons19 and 21 Status in Tissue 100 Metastatic NSCLC Patients, 1 st Line anti-egfr Therapy 30 Metastatic NSCLC Patients, Second Line Therapy 300 Matched Urine and Plasma Samples 600 Urine Samples Serial Collections on Erlotinib 210 Urine Samples Serial Collections on Second Line Therapy Evaluate EGFR Concordance between Urine and Tissue Evaluate EGFR Concordance between Plasma and Tissue ctdna Monitoring for Response and Early Acquisition of EGFR T790M EGFR T790M Concordance between Urine and Tissue *Preliminary Results 3 mon Detection of T790M 3 months prior to detection of progression by imaging* Urine vs Tissue Detection of EGFR T790M Mutation at any time point 100% 10/10 Patients Multi-Institutional Program

27 Urine Identifies More Patients with EGFR T790M Mutation than Tissue Tissue Urine 10 Patients 15 Patients Preliminary Results (Total number of patients examined by urine = 22, number of patients examined by tissue = 13 of 22) Copyright 2014 Trovagene, Inc. Confidential 27

28 Colorectal Cancer Standard of Care CLINICAL UTILTY STAGE I-III RESECTABLE STAGE IV RESECTABLE LIVER METASTASES Success of surgery Re-staging of cancer Chemo or not? ADVANCED AND METASTATIC UNRESECTABLE Replacement of biopsy performed with sole purpose of molecular diagnosis of RAS: selection of correct therapy within days of diagnosis patients go on right treatment early (anti- EGFR/ VEGFR/ BRAF or Chemotherapy?) Re-staging of cancer, response and emergence of resistance CRC Surgery Adjuvant Therapy Imaging (every 6 wks-6 months) Molecular Detection Systemic Therapy Imaging (every 6 weeks) TROVAGENE Minimal Residual Disease Response Monitoring KRAS, NRAS, BRAF Molecular Detection KRAS, NRAS, BRAF Response Monitoring KRAS, NRAS, BRAF MARKET Surgeries ~80,000 stage I-III colorectal cancer cases x 4 tests ~320,000 tests per year Molecular Detection ~50,000 stage IV ~50,000 tests 60% RAS/RAF+ 40% RAS emerging Response Monitoring ~50,000 patients per year x 4 tests ~200,000 tests Copyright 2014 Trovagene, Inc. Confidential 28

29 Colorectal Cancer Standard of Care STUDIES TROVAGENE CLINICAL UTILTY CRC STAGE I-III RESECTABLE STAGE IV RESECTABLE LIVER METASTASES Success of surgery Re-staging of cancer Chemo or not? Surgery Adjuvant Therapy Genomac (54 patients) Minimal Residual Disease Response Monitoring Imaging (every 6 wks-6 months) KRAS, NRAS, BRAF Emory (40 patients) ADVANCED AND METASTATIC UNRESECTABLE Replacement of biopsy performed with sole purpose of molecular diagnosis of RAS: selection of correct therapy within days of diagnosis patients go on right treatment early (anti- EGFR/ VEGFR/ BRAF or Chemotherapy?) Re-staging of cancer, response and emergence of resistance Molecular Detection Molecular Detection KRAS, NRAS, BRAF ONG-INBB (40 patients) Systemic Therapy MDACC (30 patients) Imaging (every 6 weeks) Response Monitoring KRAS, NRAS, BRAF USC (60 patients) MSK (200 patients) Copyright 2014 Trovagene, Inc. Confidential 29

30 Detection and Monitoring Minimal Residual Disease in Surgical Colorectal Cancer Patients with Liver Metastases 1 20 Stage IV colorectal cancer patients with resectable liver metastases KRAS mutation in tissue Matched urine and plasma, archived (3-5 years) Blinded analysis, seven KRAS mutations (G12A/C/D/R/S/V and G13D) Plasma (20 Patients) Urine (20 Patients) Plasma vs. Tissue Biopsy Concordant KRAS mutation at baseline 19/20 evaluable Urine vs. Plasma Concordant KRAS mutation at baseline 12/12 matched 95% 100% 92% Urine vs. Tissue Biopsy Concordant KRAS mutation at baseline 11/12 evaluable Serial monitoring during and post surgery (n=193 plasma and urine samples) 1 Poole et al, ASCO GI 2015

31 High Concordance btw Urine & Plasma ctdna KRAS in Resectable CRC: Monitoring During & Post Surgery 1 Curative surgery correlates with un-detectable levels of ctdna KRAS post-surgery Palliative surgery correlates with high levels of ctdna KRAS post-surgery 1 Poole et al, ASCO GI 2015

32 Pancreatic Cancer Standard of Care CLINICAL UTILTY DIAGNOSIS Screening for cancer RESECTABLE DISEASE Success of surgery Re-staging of cancer Chemo or not? ADVANCED AND METASTATIC UNRESECTABLE Prognosis of disease for determining aggressiveness of therapy Clinical trials targeting KRAS Pancreatic Cancer Diagnosis Biopsy Resectable Disease Surgery Adjuvant Therapy Imaging (every 6-12 weeks) Non-Resectable Disease Chemotherapy Imaging (every 6-12 weeks) TROVAGENE Pancreatic Cancer Screening KRAS G12/13 CA 19-9 Minimal Residual Disease Response Monitoring KRAS G12/13 Prognostic for Survival KRAS G12/13 + CA-19-9 Response Monitoring KRAS G12/13 MARKET Pancreatic Cancer Screening ~18m individuals 50 and over per year screened Minimal Residual Disease Response Monitoring ~8500 surgeries x 4 tests per patient ~34,000 tests per year Prognostic for Survival ~32,000 unresectable patients per year Response Monitoring 32,000 x 4 tests per patient ~128,000 tests per year Copyright 2014 Trovagene, Inc. Confidential 32

33 Pancreatic Cancer Standard of Care CLINICAL UTILTY DIAGNOSIS Screening for cancer RESECTABLE DISEASE Success of surgery Re-staging of cancer Chemo or not? ADVANCED AND METASTATIC UNRESECTABLE Prognosis of disease for determining aggressiveness of therapy Clinical trials targeting KRAS Pancreatic Cancer Diagnosis Biopsy Resectable Disease Surgery Adjuvant Therapy Imaging (every 6-12 weeks) Non-Resectable Disease Chemotherapy Imaging (every 6-12 weeks) TROVAGENE Pancreatic Cancer Screening KRAS G12/13 CA 19-9 Minimal Residual Disease Response Monitoring KRAS G12/13 Prognostic for Survival KRAS G12/13 + CA-19-9 Response Monitoring KRAS G12/13 STUDIES University of Copenhagen University of Copenhagen (50 patients) MDACC (90 patients) University of Copenhagen (182 patients) USOR - SH - UCSF (45 patients) University of Copenhagen (182 patients) USOR - SH UCSF (45 patients) Copyright 2014 Trovagene, Inc. Confidential 33

34 Prognostic ctdna KRAS and Serum CA19-9 in Unresectable Pancreatic Cancer 1 50 Patients with Resectable Pancreatic Cancer Surgery, Chemotherapy Plasma, archived 6 years 150 Plasma Samples: Pre-operative, Post-Surgery, Serial Collections on Chemotherapy 182 Patients with Non-Resectable Pancreatic Cancer Chemotherapy Plasma, archived 6 years 640 Plasma Samples: Baseline, Serial Collections on Chemotherapy ctdna KRAS detection at baseline for association with overall survival ctdna KRAS monitoring for response to chemotherapy ctdna KRAS and CA-19-9 detection at baseline for association with overall survival ctdna KRAS monitoring for response to chemotherapy 182 Patients KRAS < 41 copies/100k GE CA-19-9 < 314 U/mL KRAS > 41 copies /100K GE > CA-19-9 < 314 U/mL 1 Johansen et al, ASCO GI days OS (median, FOLFIRINOX) 325 days OS (median, GEMZAR) p < , HR = 3.0 (95% CI: ) 202 days OS (median, FOLFIRINOX) 127 days OS (median, GEMZAR) 34

35 Melanoma Standard of Care CLINICAL UTILTY STAGE IV METASTATIC MELANOMA Monitoring response allows selection or early switch to optimal therapy: BRAF inhibitors or Immunotherapy? Optimal intervals on intermittent BRAF therapy Immunotherapy Pseudoprogression or not? MELANOMA First Line Treatment Imaging (every 6-8 weeks) Drug Holidays Imaging (every 6-8 weeks) Second Line Treatment Imaging (every 6-8 weeks) TROVAGENE Response Monitoring BRAF MARKET Response Monitoring ~9000 stage IV patients x 60% BRAF+ x 10 tests ~54,000 tests per year Copyright 2014 Trovagene, Inc. Confidential 35

36 Melanoma Standard of Care CLINICAL UTILTY STAGE IV METASTATIC MELANOMA Monitoring response allows selection or early switch to optimal therapy: BRAF inhibitors or Immunotherapy? Optimal intervals on intermittent BRAF therapy Immunotherapy Pseudoprogression or not? MELANOMA First Line Treatment Imaging (every 6-8 weeks) Drug Holidays Imaging (every 6-8 weeks) Second Line Treatment Imaging (every 6-8 weeks) TROVAGENE Response Monitoring BRAF STUDIES DFCI (40 patients) MSKCC (50 patients) UCSF (210 patients) Georgetown University (7 patients) Copyright 2014 Trovagene, Inc. Confidential 36

37 Monitoring ctbraf V600E and Treatment Response 1 17 metastatic cancer patients Positive urine BRAF V600E 15 evaluable patients for ctdna BRAF V600E 4 weeks Urine ctdna BRAF decrease Evaluate time to progression % tumor change per RECIST 1.1 Urine ctdna BRAF increase Urine BRAF ctdna correlates to BRAF/MEK targeted therapy (p=0.002) Urine BRAF V600E ctdna monitoring has clinical utility to track therapeutic efficacy of targeted therapy in metastatic cancer patients harboring mutant BRAF V600E 259 days (median) to progression 95% CI= days 61 days (median) to progression 95% CI = days p= Janku et al, AACR

38 Longitudinal ctdna BRAF V600E Mutation Status Correlates with Therapy Response 1 Patient 8: Metastatic Non-Small Cell Lung Cancer Patient 16: Metastatic Colorectal Cancer Patient 5: Metastatic Melanoma Patient 36: Metastatic Non-Small Cell Lung Cancer Urine BRAF V600E ctdna monitoring has clinical utility to track therapeutic efficacy of targeted therapy in metastatic cancer patients 1 Janku et al, AACR

39 Ongoing Clinical Studies Continue to Drive Publications 11/2014 EORTC-NCI-AACR Abstract(s) ASCO GI 1/ abstracts accepted 8/2015 NEXTGEN DX SUMMIT 4/2015 AACR 3 abstracts submitted Submit abstract Technology 3/2015 EORTC-NCI-AACR Submit abstracts 10/2014 HISTIOCYTIC SOC. Abstract ECD/LCH BRAF MSKCC/MDACC 2/2015 EUROGIN Oral presentation 5/2015 ASCO 5 abstracts submitted Melanoma, lung, pancreatic colorectal cancers 9/2015 ESMO Submit abstracts Submit manuscript HR-HPV Method Submit manuscript Longitudinal KRAS Colorectal Submit manuscript Longitudinal KRAS Pancreatic Submit manuscript HR-HPV Predictor4 4/2015 European Lung Cancer Conference Oral presentation Submit manuscript Detection and monitoring EGFR T790M Lung Submit manuscript Longitudinal and pharmacodynamic BRAF and KRAS multiple cancers MD Anderson 9/2015 Submit manuscript KRAS/BRAF colorectal Technology comparison study IPV Conference Submit Abstracts 9/ /2015 HISTIOCYTIC SOC. Submit abstracts 16 th World Conference on Lung Cancer Submit abstracts 10/2015 Chicago Multidisciplinary Symposium in Thoracic Oncology Submit abstracts Q4 Q1 Q2 Q3 Q Copyright 2014 Trovagene, Inc. Confidential 39

40 Market Development Activities for Commercialization Program Market Development ( ) Full Commercialization (2015) Relationships w/ 30+ top cancer centers 17 National Comprehensive Cancer Network (NCCN) Centers Target KOLs/ Early adopters Develop IIS (Investigator Initiated Study) Program 100+ oncologists engaged in outreach Signed partnership w/ 2 major IDNs CHI (Catholic Health Initiative) 93 hospitals Lurie Cancer Center of Northwestern Univ. Accelerate Adoption within Integrated Healthcare Delivery Networks (IDNs) Branding, Market Awareness and Education Copyright 2014 Trovagene, Inc. Confidential 40

41 Key Components for Full Commercialization in 2015 Full Commercialization (2015) Drive Adoption of Expanded Menu Conversion of Research Collaborators to Clinical Adopters Direct sales team 6 sales reps in Phase 1 Headcount ramp to be initiated in Q Direct coverage of top target sites Major academic cancer centers Entire ECD/LCH treating physician base IDNs where TROV has relationships Geographic focus on key oncology markets Expand New Market Segments New Market for Genomic Monitoring Copyright 2014 Trovagene, Inc. Confidential 41

42 Reimbursement Value Based on Clinical Utilities of ctdna Detection of Mutation Monitoring Tumor Size When tissue biopsy is unavailable Supplement tissue biopsy to get systemic overview of the entire heterogeneity of cancer Tumor load Emergence of resistant mutations Drug holidays Once Clinical Data Established, Reimbursement: Tier 1 MDx Codes Concordance with SOC Established codes Price/assay Repeat Testing: Novel Utility 1. Not Otherwise Classified Codes (NOC) 2. Unique CPT Codes Copyright 2014 Trovagene, Inc. Confidential 42

43 Trovagene Urine-based High Risk HPV Assay Cervical Cancer HPV Testing Market Globally 265K Deaths in 2012 $6B Market in 2013 $9B Market in 2020 Urine-based High Risk HPV Assay established in Trovagene s CLIA lab since 2013 New Clinical Evidence Screening is a viable solution: 75% reduction in incidence in US from 1940 to 1980 w/ National Screening Program Screening not available globally: Cost, Technical expertise, Healthcare infrastructure, Quality Control, Cultural High-risk HPVs cause virtually all cervical cancers NCI: Comparative Urine Study J Clin Virol Aug;60(4):414-7 UNC: Urine collection methodology for detecting HPV associated with CIN2+/CIN3 Queen Mary, UL: High sensitivity of test for detecting HPV associated with CIN2+, CIN3 (malignancy) Source: Transparency Market Research Copyright 2014 Trovagene, Inc. Confidential 43

44 Developing Trovagene s HPV Franchise Internal Development 1. Clinical studies in general screening population Strand Life Sciences (3,000 patients, enrollment underway) Planning stages for pivotal studies 2. Obtain regulatory compliance Partnering Opportunities Strategic partners to commercialize the test globally CE Mark FDA Copyright 2014 Trovagene, Inc. Confidential 44

45 Catalysts & Milestones to Drive Valuation Demonstrate clinical utility Expand mutation coverage on PCM platform Initiate new collaborations to establish clinical utility Establish strategic partnerships to grow market reach Drive early adoption in top cancer centers and integrated healthcare networks 20+ abstracts and manuscripts in New Menu Assays 10+ clinical studies in 2015 Top academic centers Geographic expansion Kit manufacturing Pharma collaboration Commercial presence in 20 cancer centers with repeat revenue HPV collaboration Copyright 2014 Trovagene, Inc. Confidential 45

46 For further information Please contact: Stephen Zaniboni, CFO Antonius Schuh, CEO